HEALTH OF WOMAN. 2019.4(140): 59–63; doi 10.15574/HW.2019.140.59

Skrypchenko N., Vorobyova I., Mazur T., Tkachenko V.
SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova NAMS of Ukraine», Kiev

During pregnancy, a unique new equilibrium state appears between the systems of the specific and nonspecific mothers immunity. Besides, the cytokine cascade is launched, which includes proinflammatory and anti-inflammatory factors of influence. The balance between these two groups of mediators determines the nature of the course and outcome of the gestation process.
The objective: to determine the role of mediators of pro-inflammatory and anti-inflammatory reactions of gestation intercourse in patients with miscarriage.
Materials and methods. The main group (the first group) was made up of 153 pregnant women with miscarriage. The control group (the second group) consisted of 25 relatively healthy women with a physiological course of pregnancy and a complcated obstetric and gynecological anamnesis, with one and more physiological births in anamnesis. The concentration of cytokines IL-1 β, IL-6, IL-8, IL-10, TNF- α in the blood and their content in cervical mucus by solid-phase immune-enzyme analysis was determined.
Results. Consequences of previous pregnancies having a background of inflammatory complications of genital and extragenital genesis create conditions for long-term persistence of latent infection, including in the uterine cavity and cervical canal, followed by infection of the fetus, and contribute to the development of immune imbalance during gestation, which leads to a cascade of homeostasis disorders with the development of complications of the pregnancy intercourse and perinatal pathology. Thus, the presence of clinical symptoms of the threat of premature abortion occurs in the context of an increase in the concentration of proinflammatory cytokines (IL-6, IL-8, TNF- α and IL-1 β) in serum.Reducing the concentration of IL-10 in non-pregnant women, relative to such in control group, throughout the entire pregnancy in the blood and its content in cervical mucus indicates a violation of the balance of pro– and anti-inflammatory cytokines in the direction of pro-inflammatory reactions and violation of the local immune response.
Conclusions. In women with a loss in the first trimester there is a pro-inflammatory activity of the immune response, which is an important pathogenetic factor in the development of abortion in different gestational periods.
Key words: miscarriage, proinflammatory cytokines, anti-inflammatory cytokines.

REFERENCES

Gankovskaya OA. 2010. Molekulyarno-geneticheskie mehanizmyi vrozhdennogo immuniteta na urovne slizistyih obolochek pri patologii infektsionnogo geneza. Diss. d-ra med. nauk. M:300.

Zhuk SI, Kalinka Ya, Sidelnikova VM. 2017. Nevyinashivanie beremennosti: novyiy vzglyad na staruyu problemu. Zdorove Ukrainyi 5/1: 35.

Kokryakov VN. 2006. Ocherki o vrozhdennom immunitete. SPb, «Nauka»:261.

Lebedeva OP, Pahomov SP, Kalutskiy PV, Karpov PA, Churnosov MI, Popov VN. 2012. Rol Toll-podobnyih retseptorov vrozhdennogo immuniteta v razvitii akusherskoy i ginekologicheskoy patologii. Immunopatologiya, allergologiya, infektologiya 1: 19–26.

Alijotas-Reig J, Llurba E, Gris JM. 2014. Potentiating maternal immune tolerance in pregnancy: a new challenging role for regulatory T cells. Placenta  35:241–248. PubMed Cross Ref Google Scholar. https://doi.org/10.1016/j.placenta.2014.02.004; PMid:24581729

Ashton S, Whitley G, Dash P et al. 2005. Uterine spiral artery remodeling involves endothelial apoptosis induced by extravillous trophoblasts through Fas/FasL interactions. ArteriosclerThomb Vase Biol. 1: 102-108. PubMed Cross Ref Google Scholar. https://doi.org/10.1161/01.ATV.0000148547.70187.89; PMid:15499040 PMCid:PMC4228192

Azizieh FY, Raghupathy RG. 2015. Tumor necrosis factor-α and pregnancy complications: a prospective study. Med PrincPract. 24:165–170. Pub Med Cross Ref Google Scholar. https://doi.org/10.1159/000369363; PMid:25501617 PMCid:PMC5588217

Brogin-Moreli J, CirinoRuocco AM, Vernini JM, Rudge MV, Calderon IM. 2012. Interleukin 10 and tumor necrosis factor-alpha in pregnancy: aspects of interest in clinical obstetrics. Obstet Gynecol. 23:72-74. Google Scholar. https://doi.org/10.5402/2012/230742; PMid:22462002 PMCid:PMC3302063

Cetrone M, Parisi G, Tricarico D, Pierri CL, Bossis F, Punzi G, De Grassi A. 2016. Molecular modeling of antibodies for the treatment of TNF α-related immunological diseases. Pharmacol Res Perspect. 4:e00197. https://doi.org/10.1002/prp2.197; PMid:26977294 PMCid:PMC4777268 Pub Med Pub Med Central Cross Ref Google Scholar.

Cheng SB, Sharma S. 2015. Interleukin-10: a pleiotropic regulator in pregnancy. Am J ReoprodImmunol. 73:487–500. Cross Ref Google Scholar. https://doi.org/10.1111/aji.12329; PMid:25269386 PMCid:PMC4382460

Choi SJ, Jung SH, Eom M, Han KH, Chung IB, Kim SK. 2012. Immunohistochemical distribution of toll-like receptor 4 in preterm human fetal membrane. J Obstet Gynaecol Res. 38(1): 108-112. https://doi.org/10.1111/j.1447-0756.2011.01626.x; PMid:21827576

Grimstad F, Krieg S. 2016. Immunogenetic contributions to recurrent pregnancy loss. J Assist Reprod Genet. 33 (7):833-847. https://doi.org/10.1007/s10815-016-0720-6; PMid:27169601 PMCid:PMC4930783

Moço NP, Martin LF, Pereira AC, Polettini J, Peraçoli JC, Coelho KI, da Silva MG. 2013. Gene expression and protein localization of TLR-1, -2, -4 and -6 in amniochorion membranes of pregnancies complicated by histologic chorioamnionitis. Eur J Obstet Gynecol Reprod Biol.  171 (1): 12–17. https://doi.org/10.1016/j.ejogrb.2013.07.036; PMid:24125907

Mor G, Kwon J. 2015. Trophoblast-microbiome interaction: a new paradigm on immune regulation. American Journal of Obstetrics and Gynecology  213 (4): 131. https://doi.org/10.1016/j.ajog.2015.06.039; PMid:26428492

Moreli JB, Corrêa-Silva S, Damasceno DC, Sinzato YK, Lorenzon-Ojea AR, Borbely AU. 2015. Changes in the TNF-alpha/IL-10 ratio in hyperglycemia-associated pregnancies. Diabetes Res ClinPract. 107:362–369. PubMed Cross Ref Google Scholar. https://doi.org/10.1016/j.diabres.2015.01.005; PMid:25648390

Yuan J, Li J, Huang SY, Sun X. 2015. Characterization of the subsets of human NKT-like cells and the expression of Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion. J ReprodImmunol. 110:81–88. PubMed CrossRef Google Scholar. https://doi.org/10.1016/j.jri.2015.05.001; PMid:26057526

Schatz F, Kayisli UA, Vatandaslar E, Ocak N. 2012. Toll-like receptor 4 expression in decidual cells and interstitial trophoblasts across human pregnancy. Am J Repr Immun. 68: 146–153. https://doi.org/10.1111/j.1600-0897.2012.01148.x; PMid:22564191 PMCid:PMC3395732

Skorpen CG, Hoelzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C et al. 2016. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 75:795–810. Cross Ref Google Scholar. https://doi.org/10.1136/annrheumdis-2015-208840; PMid:26888948

Subramaniam A, Abramovici A, Andrews WW, Tita AT. 2012. Antimicrobials for preterm birth prevention: an overview. Infect. Dis. Obstet. Gynecol. 157–159. https://doi.org/10.1155/2012/157159; PMid:22505797 PMCid:PMC3296158

Winger EE, Reed JL, Ashoush S, El-Toukhy T, Ahuja S, Taranisi M. 2011. Degree of THF-α/IL-10 cytokine elevation correlates with IVF success rates in women undergoing treatment with adalimumab (Humira) and IVIG. Am J ReprodImmunol. 65:610–618. Pub Med Cross Ref Google Scholar. https://doi.org/10.1111/j.1600-0897.2010.00946.x; PMid:21223418